The present invention relates to a virus-inactivating oil-in-water emulsion which begins inactivating viruses upon contact.
It is known that if a water-immiscible liquid phase is mixed into an aqueous phase by mechanical agitation, for example, by means of an ultra-disperser, a dispersion, such as an oil-in-water emulsion, will develop. The stability of the resulting dispersion may require the addition of an emulsifying agent, the molecules of which are adsorbed onto the oil/water interface to form a kind of continuous membrane which prevents direct contact between two adjacent droplets. One advantage of oil-in-water emulsions is that they may readily be diluted with water to a desired composition.
In addition to discrete oil droplets dispersed in an aqueous phase oil-in-water emulsions can also contain other lipid structures, such as small lipid vesicles (i.e., lipid spheres which often consist of several substantially concentric lipid bilayers separated from each other by layers of aqueous phase), micelles (i.e., amphiphile molecules in small clusters of 50-200 molecules arranged so that the polar head groups face outward toward the aqueous phase and the a polar tails are sequestered inward away from the aqueous phase), or lamellar phases (lipid dispersions in which each particle consists of parallel amphiphile bilayers separated by thin films of water). These lipid structures are formed as a result of hydrophobic forces which drive apolar residues (i.e.,long hydrocarbon chains) away from water.
The portals of entry of pathogenic bacteria, viruses or fungi are predominantly the skin and mucus membranes, including the upper and lower respiratory tracts. The first step in many infections is attachment or colonization on skin or mucus membranes, followed by subsequent invasion and dissemination of the infectious pathogen. Accordingly, it is desirable to provide a virus-inactivating formulation which inactivates viruses on contact.
Detergents and solvents have been used to inactivate viruses in blood or plasma derived products, as described in U.S. Pat. No. 4,540,573 to Neurath, the contents of which are hereby incorporated by reference. This patent teaches the use of aqueous solutions of trialkylphosphates to inactivate viruses in blood-derived products in vitro. However, after treatment of the blood-derived product according to this method, the trialkyl phosphate must then be removed by methods such as dialysis or lyophilization, necessitating additional extraction steps (as described in U.S. Pat. No. 4,909,940 to Horowitz, the contents of which are hereby incorporated by reference). This lengthy and complex procedure is not suitable for use in treating viral infections in an affected subject, nor does the patent teach or suggest in vivo uses of the solutions.
Furthermore, many trialkyl phosphates are known to be toxic or irritating to mucous membranes (see, e.g., Smyth and Carpenter (1944) J Ind Hyg. Toxicol. 26: 269). For these reasons, they have not been thought to be usable in preparations intended for in vivo administration.
Accordingly, an object of the present invention is to provide a virus-inactivating emulsion which inactivates viruses on contact. It is a further object of the invention to provide a non-irritating, stable preparation that inactivates viruses, especially envelope viruses, on the skin or mucous membranes.
Another object of the present invention is to provide a method of inactivating a virus by contacting the virus with a virus-inactivating emulsion.
Another object of the present invention is to provide a method of preventing a viral infection in an affected subject by administering a virus-inactivating emulsion to the subject.